Identification and evaluation of Nordihydroguaiaretic acid (NDGA) as an active traditional Chinese medicine compound inhibiting the 3C-like protease of feline infectious peritonitis virus

  • Vet Microbiol. 2025 Sep 15:310:110730. doi: 10.1016/j.vetmic.2025.110730.
Wei Yuan  1 ,  Xiaoen Pang  1 ,  Jingru Zhu  1 ,  Zan Chen  1 ,  Shuna Li  1 ,  Zhibo Yang  1 ,  Xiaohu Zhang  1 ,  Changbin Jin  1 ,  Xintong Huang  1 ,  Yu Shen  1 ,  Huarong Fang  1 ,  Jiahao Lin  2 ,  Yueping Zhang  3
Affiliations
  • 1. National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
  • 2. National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Beijing Zhongnongda Veterinary Hospital Co., Ltd., Beijing 100193, China; Teaching Animal Hospital, China Agricultural University, Beijing 100193, China. Electronic address: [email protected].
  • 3. National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address: [email protected].
PMID: 40976146 DOI: 10.1016/j.vetmic.2025.110730
Abstract

Feline infectious peritonitis (FIP) is a systemic and fatal disease that poses a serious threat to feline population, underscoring the urgent need for development of novel Antiviral drugs. The FIP is caused by the feline infectious peritonitis virus (FIPV), a highly pathogenic feline coronavirus (FCoV), and 3C-like protease (3CLpro) is a critical drug target in coronaviruses. Here, we employed structure-based in silico screening and identified Nordihydroguaiaretic acid (NDGA), a bioactive compound used in traditional Chinese medicine, as a potential FIPV 3CLpro inhibitor. Enzymatic assays confirmed that NDGA effectively inhibits FIPV 3CLpro activity. Furthermore, cellular assays demonstrated that NDGA suppresses FIPV replication. Additionally, in a feline challenge model with an FCoV-II strain, NDGA treatment prolonged survival and improved clinical outcomes. These results support NDGA as a potential lead compound for FIP therapy.

Keywords
3C-like protease; Antiviral; Feline infectious peritonitis; Nordihydroguaiaretic acid; Traditional Chinese medicine.
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